George Van S. Smith

Prolan and estrin in the serum and urine of diabetic and nondiabetic women during pregnancy, with especial reference to late pregnancy toxemia

Abstract Analyses on 12 nondiabetic women throughout normal pregnancies indicate that the peak in prolan of both urine and serum occurs at approximately two months and that by the beginning of the fourth month this hormone reaches a lower and fairly constant level coincident with an increase in estrin. The most rapid rise in estrin of both urine and serum takes place during the last trimester. The data on 6 cases of late pregnancy toxemia (4 of them diabetics) confirm the previously reported finding of high prolan and low estrin in this condition and demonstrate that the abnormal rise in serum prolan precedes the clinical manifestations by at least six weeks . The curves on 5 diabetic women throughout normal pregnancies are essentially similar to those of the normal nondiabetics. A somewhat later rise in estrin and a less marked plateau of prolan suggests, however, that the high incidence of toxemia in diabetic pregnancies may be linked with a prolan-estrin imbalance which approaches the toxemic borderline. In 4 cases, two diabetic patients, high serum prolan at five to seven months led to the prediction of late pregnancy toxemia. One of these women (diabetic) had a premature delivery at seven and one-half months. The other 3 showed a very marked rise in estrin during the last trimester coincident with a drop in prolan to within the limits of normal and the appearance of only very mild toxic symptoms. Of the 11 diabetic patients followed, 4 had either stillbirths or edematous giant infants. All 4 of these women showed the prolan-estrin imbalance typical of toxemia at five to seven months. The diabetic patients with normal curves for prolan and estrin delivered normal, living infants. Two of the diabetic patients, on the other hand, whose prolan was excessive and who developed severe toxemia, were delivered by cesarean section at seven and one-half months of normal, living infants. Although it might be argued that in these two cases early delivery had preceded abnormal growth of the fetus, the data at hand are too limited to permit the establishment of any connection between the endocrine findings and the type of infant in diabetic pregnancies.

Progestin and Estrin of Nineteen Placentas from Normal and Toxemic Cases.

Conclusion The placentas of late pregnancy toxemia cannot be shown by the methods available to differ significantly in content of progestin from those of non-toxemic pregnancy.

Pituitary Stimulating Property of Stilbestrol as Compared with That of Estrone.

Summary Stilbestrol is about 100 times as active as estrone in causing the stimulation and release of adrenotropic and gonadotropic factors from the pituitaries of intact mature male rats. In castrated animals it is only about twice as active as estrone. Unlike estrone, the pituitary responses to stilbestrol are not influenced by the presence of the testes or the administration of progesterone, both of which depress the rate of inactivation of estrone as well as its pituitary stimulating activity. It would appear that the mechanism of stil-bestrols action upon the pituitary differs from that of the naturally-occurring estrogens.

Menstrual Discharge of Women. I. Its Toxicity in Rats.

Conclusion The menstrual discharge of women with normal cycles is highly toxic to rats through the production of vascular damage. The possibility that this toxicity is accountable to protein decomposition has not been conclusively ruled out, although the marked effect of hormonal conditions upon resistance appears to argue against this. The greatest susceptibility requires the presence of the ovaries. Functional corpora lutea afford partial protection, but the administration of estrogen overrides this action. Protection may be rendered by pretreatment with large amounts of progesterone, adrenal cortical extract or “immune” rabbit serum. The toxin appears to be intimately associated with a large moleculed protein material.

Evidence that Menstrual “Toxin” and Canine “Necrosin” are Identical:

Conclusion Physical, chemical, and biological similarities, cross precipitin tests and experiments on transferable immunity indicate that Menkins so-called necrosin of canine pleural exudates and the toxin of human menstrual discharge are identical.

Evidence for Circulating Menstrual “Toxin” During Menstruation and Toxemia of Late Pregnancy

Conclusion Serum from the circulating blood of women during menstruation and toxemia of late pregnancy differs from that of normal non-menstruating and normally pregnant women and resembles menstrual “toxin” in that it is pyrogenic and fibrinolytic, gives positive precipitin tests with the serum of rabbits immunized against cannie “necrosin,” and contains a pseudoglobulin capable of prolonging the survival time of rats after a lethal dose of menstrual toxin. It is concluded that a factor identical to menstrual “toxin” is present in the circulating blood of menstruating and toxemic women. The protective factor is being further investigated as to its possible therapeutic applications.

Carcinoma of the Uterine Cervix

Abstract Eleven hundred and eleven consecutive, previously untreated, pathologically confirmable cases of cancer of the uterine cervix are reviewed. The percentages of patients who were alive five years after first treatment are as follows: 1902 to 1913, 12; 1914 to 1918, 19; 1919 to 1923, 23; 1924 to 1928, 28; 1929 to 1933, 38; 1934 to 1938, 43. The percentages of patients alive at ten years in the same groups to 1934 are: 7, 11, 12, 21, and 29. The percentages of patients alive at fifteen years to 1929 are: 7, 9, 8, and 15. The improved results are due for the most part to the use of radium and x-rays. Seventy-one per cent of the patients alive five years after treatment were alive at ten years, and 75 per cent of those alive at ten years were alive at fifteen years. Two patients had proved recurrence between thirteen and fourteen years after irradiation. Deaths, early and late, from treatment and intercurrent disease are listed. Complications and their treatment are given considerable attention, since they are such an important part of radiation therapy. Four patients had another primary cancer at the time that of the cervix was treated and six later developed primary malignancies, two of which occurred in organs previously irradiated, namely, bladder and rectum. Of the whole series of 1,111 patients, 5.2 per cent had had a previous supravaginal hysterectomy and 2.7 per cent more had had tubes or ovaries or both removed or tubal ligation.

Clinical experiments in relation to the excretion of the estrogens

Abstract Urinary studies in a patient with severe pre-eclampsia during a fourday period when veratrum viride was given have shown that the excretion of estrogen metabolites is markedly affected by the temporary vasodilatation caused by this drug. The findings indicate a sudden decrease in degradation and increased metabolic conversion of the estrogens. The hormonal effects are of as short duration as are the clinical. There is reason to suppose that the relationship between sex steroid production and metabolism and genital vascular supply is reciprocal. The etiologic and therapeutic implications of this finding are discussed.

Menstrual Discharge of Women. II. Its Progesterone-Stimulating Effect in Mature Rats.

Conclusion The menstrual discharge of normally menstruating women contains a heatstable factor, insoluble in lipoid solvents, which stimulates increased luteal activity in mature rats. This factor has also been found in venous blood and urine at the time of menstruation. Its progesterone-stimulating effect is not accountable to any free or combined estrogen or to any known gonadotropic hormone. So far as this work has progressed, the progesterone-stimulating factor of menstrual discharge resembles the substance reported by Astwood and Greep as occurring in the rat placenta. 4 Our material has not yet been tested upon hypophysectomized rats but the fact that alcohol precipitation destroys toxicity without decreasing progesterone-stimulating activity makes it appear that the progesterone stimulation is not a non-specific toxic effect.

Ten cases of Brenner tumor of the ovary

Abstract Ten cases of Brenner tumor of the ovary have been presented, the diagnosis of seven of which has been confirmed by R. Meyer. The clinical and pathologic findings have been summarized and briefly discussed.